tbuckley/cabot-search huggingface dataset:
PB2485: INVESTIGATING THE EXPRESSION OF MUCIN-1 (MUC-1) DURING ERYTHROID DIFFERENTIATION
Authors: Hammad Hassan, Sarah Yousuf, Areeb Ahmed, Afsar Mian, Sheerien Rajput
Journal: HemaSphere (2023)

Topic: 23. Hematopoiesis, stem cells and microenvironment Background: MUC1 is a type 1 trans membrane glycoprotein expressed on the apical surface of polarized epithelia as well as non-epithelial cell surfaces such as hematopoietic cells. Expression of MUC1 has been identified in 2-10% of normal human BM mononuclear cells, CD34+cells, resting T cells, splenic and tonsillar B cells and plasma cells. Its expression in hematopoietic cells suggest its non-epithelial function. Although circulating erythrocytes are completely negative for MUC1 expression; transient expression of MUC1 has been reported previously in CD34 positive cells undergoing erythroid lineage differentiation in vitro. These findings indicate the potential role of MUC1 during in vitro erythropoiesis. However, its specific expression and function during erythroid differentiation remains unclear. This study investigates the expression of MUC1 in erythroid differentiation in vitro using K562 cell line model. Aims: The aim of this study was to investigate the expression of MUC-1 during erythroid differentiation in vitro using Asciminib as a potential inducer of erythroid lineage. Methods: The erythroleukemic cell line, K562 is a widely used model for studying erythroid differentiation in vitro. We cultured K562 over 6-days in Erythropoietin (EPO)-based diﬀerentiation media containing Imatinib (400nm), asciminib (20nM) or combination of both. Asciminib is a novel allosteric inhibitor of BCR-Abl and a potential inducer of erythroid differentiation. Observations were recorded at days 3 and 6 following induction of erythroid differentiation. We analyzed the expression of CD235a and CD71 surface markers using flow cytometry to determine the degree of diﬀerentiation achieved. To identify hemoglobin producing cells ensuing diﬀerentiation, benzidine staining was undertaken at particular time points. mRNA and protein expression of MUC-1 during erythroid differentiation was evaluated using RT-PCR analysis. Results: EPO-based diﬀerentiation media supplemented with Imatinib, Asciminib or combination resulted in eﬃcient erythroid diﬀerentiation with high levels of GPA expression (approx. 90%) and significant upregulation of globin genes (p value < 0.001). Furthermore, cells undergoing erythroid lineage differentiation showed MUC1 downregulation at mRNA and protein levels. Summary/Conclusion: We have established a robust erythroid differentiation protocol using imatinib and asciminib. Our data confirms that MUC-1 expression is down-regulated during erythroid differentiation. Further studies are needed to fully understand the molecular mechanisms through which MUC1 regulates erythroid differentiation, and its potential as a therapeutic target in erythroid disorders.Keywords: Erythropoieisis, Erythropoietin, Erythroid differentiation, Erythroid lineage
P1550: HAEMATOLOGICAL PREDICTORS OF POOR OUTCOME AMONG COVID-19 PATIENTS ADMITTED TO AN INTENSIVE CARE UNIT OF A SOUTH AFRICAN TERTIARY HOSPITAL
Authors: Zivanai Cuthbert Chapanduka, Ibtisam Abdullah, Brian Allwood, Coenraad Koegelenberg, Elvis Irusen, Usha Lalla, Annalise Zemlin, Peter Nyasulu
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Studies from Asia, Europe and the USA indicate that widely available haematological parameters could be used to determine the clinical severity of Coronavirus disease 2019 (COVID-19) and predict management outcomes. There is limited date from Africa on their usefulness in patients admitted to intensive care units (ICUs). We performed an evaluation of baseline haematological parameters as prognostic biomarkers in ICU COVID-19 patients. Aims: To evaluate baseline “routine” haematological parameters in patients admitted to the ICU of a tertiary academic hospital during the first and second COVID-19 waves and correlate these to the disease severity and outcome. Methods: Demographic, clinical and laboratory data were collected prospectively on patients with confirmed COVID-19, admitted to the adult ICU at Tygerberg Hospital, the 1384 bed teaching hospital for Stellenbosch University Faculty of Medicine and Health Sciences. The study period was March 2020 to February 2021. Robust Poisson regression methods and receiver operating characteristic (ROC) curves were used to explore the association between haematological parameters and COVID-19 severity and mortality. Results: A total of 490 patients (median age 54.1 years) were included of whom 237(48%) were female. The median duration of ICU stay was 6 days and 309/490 (63%) patients died. Raised neutrophil counts and neutrophil/lymphocyte ratios (NLR) were associated with worse outcomes. Independent risk factors associated with mortality were age (ARR 1.01, 95% CI 1.0-1.02; female sex (ARR 1.23, 95% CI 1.05-1.42; p=0.008) and D-dimer levels (ARR 1.01, 95% CI 1.002-1.03; p=0.016). Summary/Conclusion: Our study showed that raised neutrophil count, NLR and D-dimer at the time of ICU admission were associated with higher mortality. Contrary t what has been previously reported, our study revealed that females admitted to the ICU had a higher risk of mortality than males. Keywords: COVID-19, Neutropenia, Lymphocyte, Prognostic factor
LAST-seq: single-cell RNA sequencing by direct amplification of single-stranded RNA without prior reverse transcription and second-strand synthesis
Authors: Jun Lyu, Chongyi Chen
Journal: Genome biology (2023)

Existing single-cell RNA sequencing (scRNA-seq) methods rely on reverse transcription (RT) and second-strand synthesis (SSS) to convert single-stranded RNA into double-stranded DNA prior to amplification, with the limited RT/SSS efficiency compromising RNA detectability. Here, we develop a new scRNA-seq method, Linearly Amplified Single-stranded-RNA-derived Transcriptome sequencing (LAST-seq), which directly amplifies the original single-stranded RNA molecules without prior RT/SSS. LAST-seq offers a high single-molecule capture efficiency and a low level of technical noise for single-cell transcriptome analyses. Using LAST-seq, we characterize transcriptional bursting kinetics in human cells, revealing a role of topologically associating domains in transcription regulation.
PB2594: BACTEREMIA AND FEBRILE NEUTROPENIA IN PATIENTS TREATED FOR ACUTE LEUKEMIA
Authors: Bizid Inaam, Rakez Rim, Marrakchi Wafa, Wiem Boufrikha, Adnene Laatiri
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Acute leukemia represents a risk factor for profound and prolonged neutropenia. This state of immunosuppression exposes the patient to severe bacteremia, which is a major cause of morbidity and mortality. Therefore, rapid and adequate management with empirical and appropriate antibiotic therapy is essential. Aims: The purposes of this study are to describe the clinical and biological characteristics of bacteremia associated with febrile neutropenia in patients treated for acute leukemia, to study the resistance profile of the isolated bacterial strains and to evaluate the prescription of empirical antibiotic therapy in our department. Methods: This was a retrospective descriptive and monocentric study of bacteremia occurring in patients with febrile neutropenia treated for acute leukemia, conducted at the Hematology Department in the University Hospital of Monastir (Tunisia) between April 2019 and June 2021. Results: Our study included 27 patients. Forty-eight percent of them had acute myeloid leukemia. The median age was 31 years (range: 2 - 64 years). Fever was the only clinical sign in 48% of febrile neutropenia episodes. Veinitis was the most frequent clinical localization in the bacteremia episodes (29.6% of cases). Eleven percent of the bloodstream infections were associated with sepsis initially, of which seven percent had progressed to septic shock. At the onset of fever, neutropenia was profound (neutrophils < 100/mm3) in 63% of cases and prolonged (duration > 7 days) in 37% of cases. Fifty-four bacteremia were included in our study, in which 67 germs were identified. In fact, 15% of the bacteremia were polymicrobial. A predominance of Cocci Gram-Positive bacteremia compared with Gram Negative ones was observed (68.7% vs. 29.8%). Coagulase-negative Staphylococci was the most frequently detected Gram-Positive germ with resistance to methicillin noted in 68% of cases, whereas Escherichia coli and Klebsiella pneumoniae were the most common Gram-Negative strains. Extended-spectrum beta-lactamase–producing Enterobacteriaceae were identified in 17% of the blood stream infections due to Gram-negative bacteria. Compared to the European Conference on Infections in Leukemia (ECIL) and to the Infectious Diseases Society of America (IDSA) recommendations, the prescription of the first-line antibiotics in our department was appropriate in 76% of cases. However, it was effective in only 44% of cases. According to this study, we were able to validate the prescription of piperacillin tazobactam as an empirical monotherapy to treat febrile neutropenic patients in our department. Summary/Conclusion: Although compliance with the international recommendations in therapeutic conduct remains essential, the prescription of antibiotics must be guided by the ecology of each department and adapted according to the resistance profile of the isolated germs. Keywords: Infection, Acute leukemia
P1665: USE OF DOACS IN THE MANAGEMENT OF UPPER EXTREMITY DEEP VENOUS THROMBOSIS; A SYSTEMATIC REVIEW
Authors: Sarah Ge, Ali Eshaghpour, Nathalie Loeb, Saif Ali, Mark Crowther
Journal: HemaSphere (2023)

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: Upper extremity deep venous thrombosis (UEDVT) is increasing in prevalence and often provoked by unique risk factors determining its incidence and recurrence. While direct oral anticoagulants (DOACs) remain the cornerstone of lower extremity DVT management, its efficacy and safety in UEDVT remain unclear as such events were excluded from clinical trials leading to DOAC approval. Aims: To synthesize primary evidence on the clinical efficacy and safety profile of DOACs in UEDVT. Methods: We conducted a search of MEDLINE, Embase, Scopus, conference proceedings and clinical trial registers from inception to October 2022. We included randomized controlled trials (RCTs) and cohort studies of DOACs compared with conventional treatment. Two reviewers screened and extracted data at title/abstract and full-text levels individually and in duplicate. The relative risk of recurrent VTE and bleeding events were then estimated using a fixed effect meta-analysis. Results: Of the 2224 articles screened, 3 retrospective and 2 prospective cohort studies including 451 patients were selected. The included DOACs are rivaroxaban, apixaban and edoxaban; conventional treatment consisted of low molecular weight heparin and vitamin K antagonists. There was no statistically significant difference between DOACs and conventional treatment for the risk of recurrent VTE (RR 0.95, 95% CI 0.35-2.57), major bleeding (RR 0.5, 95% CI 0.12-2.13), and clinically relevant non-major bleeding (RR 0.94, 95% CI 0.36-2.44). DOACs may reduce the risk of major bleeding in comparison with conventional treatment. No heterogeneity was found across trials. Summary/Conclusion: DOACs seem as effective as conventional treatment in the management of UEDVT and there is a trend towards decreased major bleeding. Use of DOAC in patients with UEDVT may be favored given their ease of administration and fewer monitoring requirements. RCTs in this area are needed given the limited evidence available.Keywords: Anticoagulation, DVT
P1422: PREVALENCE AND RISK FACTORS FOR RETINOPATHY IN SICKLE CELL DISEASE
Authors: Kate Gardner, Sara Stuart-Smith, Arne Dekreuk, Sheila Azoujibenjamin, Dale Seviar, Rachel Kesse-Adu
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: The UK “natural history study” is a real-world multi-site study of adults with sickle cell disease (SCD) in the UK collecting all standard-of-care clinical data. After12 months, 241 individuals have been recruited: mean age 40.5 (std dev 13.9, range 8-79) with 149 (61.8%) female, and with sickle genotype: 156 HbSS (64.7%), 73 (30.3%) HbSC, 11 (4.6%) HbSB+ thal and 1 (0.4%) HbSHPFH. Retinopathy is one of the commonest sites of end organ damage in SCD but little is known about factors increasing the risk of developing retinopathy. All patients are offered annual retinal screening in specialist eye clinics: 183/241 have been screened. Aims: To investigate the prevalence and risk factors for development of sickle retinopathy. Methods: Clinical history, treatment history, admission rate, laboratory variables, steady state observations were assessed in univariate logistic analysis (with age and sex as cofactors), and significant results compared in a multivariate logistic analysis. Prior to assessment, non-normal data were transformed to a normal distribution for analysis. Results: 111 of 183 individuals assessed (60.7%) had evidence of retinopathy. Univariate analysis results are in the table. Risk of retinopathy is increased in: HbSC (49/61) compared to HbSS (61/115) (p<0.001), males (51/68) compared to females (59/108). Rising age was associated with increased risk of retinopathy. When analysing by age groups, there were similar prevalence rates in the 30-50 and >50 age groups. Increased risk of retinopathy was also associated with lower HbF% and lower transferrin saturations. Notably, there was no association with BMI, oxygen saturations, full blood counts, renal function markers, haemolytic markers, diabetes mellitus, hypertension, markers of disease severity. Multivariate analysis: Only HbF%, age, sex remained significant in multivariate analysis, see table. Summary/Conclusion: Male sex, rising age and low HbF% genotype are all associated with increased risk of sickle retinopathy in a multivariate analysis. Age analysis but subgroups suggested that, if individuals acquire retinopathy, then this is typically done by age 30-50 years rather than having an ongoing risk in later years. Low HbF% is much more commonly seen in HbSC than HbSS genotypes and raises the question that, in HbSC, it is the absence of HbF%, not a higher total Hb or the presence of HbC%, which gives rise to increased risk of retinopathy. HbF% results are steady-state results including both patients with high native HbF% and those with higher HbF% induced by hydroxycarbamide. It also provides some observational evidence that hydroxycarbamide could be considered to prevent/treat sickle retinal change. These data remind clinicians to promote retinal screening to otherwise seemingly “mild” patients with SCD.Keywords: Sickle cell disease, Sickle
PB2456: SURVIVAL OF MULTIPLE MYELOMA PATIENTS YOUNGER AND OLDER THAN 60 YEARS AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Ivan Kostroma, Ruzilja Sabitova, Zhanna Sidorova, Victoria Yudina, Stanislav Bessmeltsev, Sergey Sidorkevitch, Sergey Gritsaev
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: A cautious attitude towards patients with multiple myeloma (MM) over 60 years of age as potential candidates for autologous hematopoietic stem cell transplantation (AutoHSCT) is often due to low somatic status and/or the presence of comorbidities that increase the likelihood of developing severe complications after high-dose chemotherapy. Improving the somatic condition, resolving comorbidities, and improving the quality of life in the case of effective therapy expands the possibilities for performing AutoHSCT in older people. Aims: Comparative analysis of survival of patients with MM in groups ≤ 60 years and ≥ 61 years. Methods: A retrospective analysis of the results of AutoHSCT was carried out in 107 patients, of which 78 were ≤60 years of age and younger and 29 patients were 61 years of age and older. Results: There were no differences between the groups in terms of drugs used in the induction period, response variant and MRD negative status before AutoHSCT. In the first group, cyclophosphamide at a dose of 3 g/m/2 was significantly more frequently used as a mobilization regimen: 29.5% vs 6.9% in the second group; p=0.014. The Mel200 conditioning regimen was significantly more frequently prescribed in the first group (66.7% vs 44.8%; p=0.039), while the Mel140 regimen was used more frequently in the second group (31.1% vs 10.3%; p=0.009). The number of patients receiving G-CSF in the post-transplant period was the same: 85.9% and 93.1%, respectively. There were no differences in the number of febrile patients (70.5% vs 65.5%, respectively). The number of patients requiring transfusions of donor erythrocytes (33.3% and 31.0%, respectively) and platelet concentrate (98.7% and 96.6%, respectively) did not differ. The difference in the number of transfused doses in the groups was not significant: donor erythrocytes 1 dose vs 2 doses, respectively, and platelet concentrate 2 doses vs 3 doses, respectively. The median PFS in group 1 was 30 months vs 47 months in group 2; p=0.704. The median overall survival in the groups was 57 months vs not achieved, respectively; p=0.577. Summary/Conclusion: The comparable survival rate of MM patients under the age of 70 years justifies the expediency of increasing the number of patients of the older age group who can undergo AutoHSCT by improving the general somatic status and improving the functional state of vital organs against the background of adequately chosen therapy and choosing appropriate modes of mobilization and conditioning. Keywords: Multiple myeloma, Autologous peripheral blood stem cell tansplantati
P1462: NEUROCOGNITIVE FUNCTION AND PSYCHOLOGICAL ASSESSMENT IN TRANSFUSION-DEPENDENT BETA-THALASSEMIA PATIENTS: RELATION TO BRAIN IRON CONTENT
Authors: Amira Adly, Eman Ismail, Nouran Salah, Ghada Ibrahim, Somaia Ahmed
Journal: HemaSphere (2023)

Topic: 27. Thalassemias Background: Neurological complications in β-thalassemia patients remain subclinical and detected only during neuroimaging evaluation. Cognitive impairment, abnormal findings on evoked potentials and cerebrovascular disease comprise the broad spectrum of neurological involvement. Aims: This study assessed association between central iron overload and neurocognitive function in transfusion-dependent β-thalassemia patients. Methods: Thirty children and adolescents with β-thalassemia were enrolled and compared with 30 age- and sex-matched healthy controls. Patients were studied stressing on transfusion history, chelation therapy, markers of hemolysis and serum ferritin. Brain magnetic resonance imaging (MRI) was performed and brain R2* values of both caudate and thalamic regions were calculated. Neurocognitive functions were assessed using Stanford-Binet Test. Psychological evaluation was done using Taylor Manifest Anxiety and Deck Depression Inventory. Results: Seventeen (56.7%) β-thalassemia patients had under-threshold intelligence quotient (IQ), 36.7% had anxiety and 63.3% had moderate to severe depression. The total IQ was significantly lower among transfusion-dependent β-thalassemia patients compared with healthy control. Right and left thalamus R2* as well as right and left caudate R2* were significantly higher in β-thalassemia patients while T2* values were decreased compared with controls. β-thalassemia patients with borderline and low average IQ had higher right and left thalamus R2* as well as right and left caudate R2* values. Right and left thalamus R2* as well as right and left caudate R2* were negatively correlated to total IQ. Right and left caudate R2* were positively correlated to transfusion index, duration of chelation and liver iron concentration (LIC). Summary/Conclusion: Children and adolescents with β-thalassemia have impaired cognitive functions which may be related to the presence of subclinical levels of brain hemosiderosis. Cognitive function in those patients and brain imaging should be done as early as possible for early detection of neurological complications. Keywords: CNS, Children, beta thalassemia
PB2593: ESTABLISHING THE VACCELERATE SITE NETWORK: CAPACITY MAPPING OF CLINICAL TRIAL SITES
Authors: Jon Salmanton-García, Pauline Wipfler, Gustav Vella, Sanne Hofstraat, Patricia Bruijning-Verhagen, Oliver A. Cornely
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: The clinical research network VACCELERATE established the VACCELERATE Site Network, a platform for clinical trial sites mapping. The Site Network is organized and coordinated within the communication platform ClinicalSite (https://clinicalsite.org/). Aims: Acting as an information broker between sites and sponsors, the ultimate aim of the Site Network is to boost the conduct of clinical trials across country borders. Methods: The Site Network is open for registration for all clinical trial sites in Europe, with a worldwide expansion planned. Sites can participate by applying to the VACCELERATE Coordination Office ([email protected]), receiving access to ClinicalSite. ClinicalSite is a platform for information and data exchange between stakeholders in clinical trials, adapted to support the needs of the Site Network. Site information such as location and type of organization, information about previous experience conducting (vaccine) clinical trials, available infrastructure and preferences, as well as certificates for site and staff can be stored and updated by designated persons in respective partnership spaces. A certification system was set up to prioritize qualified, experienced and motivated trial sites and encourage inexperienced trial sites to improve their qualification. Uploading current GCP certificates and investigator CVs, experience in vaccine trials and cooperating certified laboratories is awarded with different levels of certification badges. To also conduct capacity building, VACCELERATE offers online courses to the sites. Once, the uploaded certificates are reviewed, the corresponding certification badge is available for download. ClinicalSite offers the option to share documents such as SOPs and to request a read receipt. Results: A network of capable clinical trial sites in Europe has been built and is constantly expanding, with 487 sites in 39 countries as of January 2023. It has been employed for 21 requests from vaccine developers as well as for scientific surveys, allowing a better understanding of pandemic situations from a trial site’s perspective. Summary/Conclusion: The capacity mapping performed by the ClinicalSite tool within the VACCELERATE Site Network enables functional matching of clinical trial sites with sponsors. The platform provides necessary functions to collect relevant information and organize the trial sites according to their capabilities, alongside other quality assessment tools developed within VACCELERATE. Keywords: Vaccination, Treatment, Clinical trial